Trial Outcomes & Findings for Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD (NCT NCT02685293)
NCT ID: NCT02685293
Last Updated: 2019-08-28
Results Overview
Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period. RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
TERMINATED
PHASE3
4 participants
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
2019-08-28
Participant Flow
Subjects with moderate to severe chronic obstructive pulmonary disease (COPD) were enrolled into this 2-period, 2-treatment, crossover study from 09 December 2016. The study was terminated early on 20 June 2018.
Subjects were randomly assigned, in a 1:1 ratio, to receive either Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) then Placebo MDI or Placebo MDI then GFF MDI in two 7-day treatment periods, separated by a washout period of between 7 and 21 days.
Participant milestones
| Measure |
GFF MDI, Then Placebo MDI
Subjects first received GFF MDI (PT003) 14.4/9.6 micrograms (μg) as 2 inhalations twice daily (BID) for 7 days in treatment period 1. After a washout period, subjects then received Placebo MDI as 2 inhalations BID for 7 days in treatment period 2.
|
Placebo MDI, Then GFF MDI
Subjects first received Placebo MDI as 2 inhalations BID for 7 days in treatment period 1. After a washout period, subjects then received GFF MDI 14.4/9.6 μg as 2 inhalations BID for 7 days in treatment period 2.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
1
|
3
|
|
Treatment Period 1
COMPLETED
|
1
|
3
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Washout Period
STARTED
|
1
|
3
|
|
Washout Period
COMPLETED
|
1
|
3
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
1
|
3
|
|
Treatment Period 2
COMPLETED
|
1
|
3
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD
Baseline characteristics by cohort
| Measure |
All Randomized Subjects
n=4 Participants
All subjects randomized to receive treatment.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period. RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8
|
6.10 cm^3/m^2
Standard Deviation 7.69
|
-7.93 cm^3/m^2
Standard Deviation 8.64
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of LVSV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8
|
8.40 cm^3
Standard Deviation 14.14
|
2.88 cm^3
Standard Deviation 12.61
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of RVSV, phase contrast from pulmonic valve, was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8
|
8.38 cm^3
Standard Deviation 12.74
|
2.83 cm^3
Standard Deviation 12.40
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of Pulmonary Artery Velocity was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8
|
0.91 cm/second
Standard Deviation 1.67
|
-0.15 cm/second
Standard Deviation 1.43
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of left ventricular (LV) volume was performed using MRI using LV end diastolic volume (LVEDV), 2-3 hours after dosing of Day 8 of each treatment period. LVEDV was normalized to BSA to provide the indexed counterpart (LVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8
|
6.95 cm^3/m^2
Standard Deviation 6.47
|
-1.77 cm^3/m^2
Standard Deviation 6.44
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of cardiac output was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8
|
0.95 Liters/minute
Standard Deviation 0.80
|
0.38 Liters/minute
Standard Deviation 1.17
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: Due to early termination of the study, data for this endpoint were not collected.
Assessment of PVR was performed by impedance cardiography at 30 and 60 minutes after dosing on Day 8 of each treatment period. Baseline for was defined as the average of the subject values obtained pre-dose on Day 1 of each treatment period.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects
Assessment of PA:A was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Pulmonary Artery/Aortic Diameter Ratio (PA:A) at 2-3 Hours Post-dose on Day 8
|
-0.03 ratio
Standard Deviation 0.15
|
-0.04 ratio
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: Due to early termination of the study, data for this endpoint were not collected.
Assessment of LAEDV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: Due to early termination of the study, data for this endpoint were not collected.
Assessment of LAESV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: Due to early termination of the study, data for this endpoint were not collected.
Assessment of LAEF was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of LV volume was performed using MRI using LV end systolic volume (LVESV), 2-3 hours after dosing on Day 8 of each treatment period. LVESV was normalized to BSA to provide the indexed counterpart (LVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVi) at 2-3 Hours Post-dose on Day 8
|
2.68 cm^3/m^2
Standard Deviation 2.56
|
-3.18 cm^3/m^2
Standard Deviation 2.06
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of RV volume was performed using MRI using RV end systolic volume (RVESV), 2-3 hours after dosing on Day 8 of each treatment period. RVESV was normalized to BSA to provide the indexed counterpart (RVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Right Ventricular End Systolic Volume Index (RVESVi) at 2-3 Hours Post-dose on Day 8
|
1.92 cm^3/m^2
Standard Deviation 5.95
|
-9.23 cm^3/m^2
Standard Deviation 4.64
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of PIAo was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Pulsatility Index Aorta (PIAo) at 2-3 Hours Post-dose on Day 8
|
-0.63 percent
Standard Deviation 13.45
|
-0.37 percent
Standard Deviation 4.07
|
SECONDARY outcome
Timeframe: Baseline and Day 8 of either treatment period 1 or 2, as applicable.Population: All randomized subjects.
Assessment of PAPi was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
Outcome measures
| Measure |
GFF MDI
n=4 Participants
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo MDI
n=4 Participants
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Pulmonary Artery Pulsatility Index (PAPi) at 2-3 Hours Post-dose on Day 8
|
3.60 percent
Standard Deviation 10.86
|
-4.95 percent
Standard Deviation 19.54
|
Adverse Events
GFF MDI
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
GFF MDI
n=4 participants at risk
GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
Placebo
n=4 participants at risk
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/4 • Adverse events were collected from screening, throughout the treatment periods until the follow-up visit 14±2 days from the last study treatment administration. Overall timeframe of up to a maximum of 12 weeks.
|
25.0%
1/4 • Number of events 1 • Adverse events were collected from screening, throughout the treatment periods until the follow-up visit 14±2 days from the last study treatment administration. Overall timeframe of up to a maximum of 12 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER